We have continued studies utilizing ultraviolet light (uv) induced reactivation of herpes simplex virus (HSV) infections in humans. Further analysis of data from a study of acyclovir for the prevention of UV light-induced reactivation of HSV-2 infections has revealed that UV is a potent stimulus to reactivation, inducing HSV-2 infections following 54% of first exposures to UV light. The stimulus appeared to induce recurrences primarily at the site of UV exposure with an average time to recurrence of 4.8 +/- 0.3 days (mean+/- SE). Treatment with acyclovir markedly reduced the rate of reactivation, suggesting that selected patients may benefit from taking acyclovir to prevent HSV recurrences during periods of high risk of reactivation. These results demonstrate the utility of the UV model for studying the pathogenesis of HSV reactivation and assessing anti-viral efficacy. Studies to determine the efficacy of sunblocking agents in the prevention of UV light-induced reactivation of herpes labialis have recently been completed and data is presently being analyzed. Collaborative studies with Dr. Yvonne Bryson at the UCLA Medical School, Los Angeles, have been underway to assess the ability of various epithelial irritants to produce reactivation of perigenital HSV-2 infections. Application of 0.3% anthralin/acetone under occlusion produced an erythema of comparable duration and intensity to that following UV light exposure, but the rate of HSV reactivation was only 10% as compared to a rate of 40% following UV light exposure. However, repeated application of tape to the skin produced mild erythema and a rate of reactivation of 46% demonstrating for the first time that minor trauma to the skin can produce recurrent HSV lesions.